This K-23 award application is designed to enhance the candidate's research expertise in the area of alcohol dependence (AD) co-occurring with bipolar disorder (BD). As many as 60% of bipolar patients have lifetime alcohol and substance use disorders. These patients have a more severe course of illness, marked by greater service utilization, more suicidality, more severe mood symptoms, increased violence, poor treatment adherence, and lower functioning. Remarkably, only one randomized controlled trial published to date has studied the treatment of AD when it co-occurs with BD in adults. Topiramate decreases drinking in a non-psychiatrically ill, alcohol-dependent population, but the efficacy of topiramate for AD in patients with BD is unknown. The goal of the proposed project is to study the efficacy and safety of adjunctive topiramate treatment of AD in patients with bipolar I or II disorder in a randomized, placebo-controlled trial. The primary hypothesis is that subjects randomized to topiramate will have a lower proportion of heavy drinking days at the completion of the trial compared to the placebo group. [unreadable] [unreadable] The training plan includes mentoring and consultation from experts in alcohol and substance abuse and BD, as well as biostatistics pertaining to clinical trial design and analysis. Dr. Roger Weiss, Clinical Director of the Alcohol and Drug Abuse Treatment Program at McLean Hospital, is the mentor. Dr. Joseph Calabrese, the Co-Director of a Health Research Services Administration's Center of Excellence for the Care and Study of Patients with Bipolar Disorder Comorbid with Drug and Alcohol Abuse, and Dr. Andrew Nierenberg, the PI of the Bipolar Trials Network of the NIMH, are co-mentors. Dr. Bankole Johnson, the PI of trials of topiramate for AD, and Dr. Ihsan Salloum, the PI of a trial of sodium divalproex for AD and BD, are consultants. The didactic component of the application will specifically include coursework in research design, advanced biostatistics, and research ethics. In addition to providing important data for the treatment of AD with BD, this project award will facilitate the candidate's transition to an independent investigator able to conduct clinical trials in AD and co-occuring mood disorders. Bipolar Clinic and Research Program, Massachusetts General Hospital; Boston, MA [unreadable] [unreadable] [unreadable]